The Role of the Deubiquitylase MYSM1 During Alphavirus Infection Amer Nubgan The members of the genus Alphavirus are positive-sense RNA viruses and it is one of two within the family Togaviridae. Most alphaviruses are predominantly transmitted to susceptible vertebrates by a mosquito vector. Alphavirus disease in humans can be severely debilitating, and depending on the particular viral species, infection may result in encephalitis and possibly life threatening symptoms. Chikungunya virus (CHIKV) is the aetiological agent represents a substantial health burden to affected populations, with clinical symptoms that include severe joint and muscle pain, rashes, and fever, as well as prolonged periods of disability in some patients. In recent years, CHIKV has received significant attention from public health authorities as a consequence of the dramatic emergence infections in the Indian Ocean islands and the Caribbean as well as the recent emergence of CHIKV in the Americas. Infections have also been reported around Europe such as in Italy, France and Greece. Currently, no safe, approved or effective vaccine or treatment exists for CHIKV infection. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates different kinds of cellular processes, which may be targeted by viruses to aid their replication within cells. In recent years it has been well established that both the forward reaction of ubiquitination, and the reverse reaction of deubiquitination are targeted during virus infection to enhance their replication, either by targeting of cellular proteins or encoding viral homologues of key pathway proteins. The reverse reaction is undertaken by a large family of enzymes termed deubiquitylases or DUBs, and many of these have been shown to play a crucial role, not only in virus replication but also in the regulation of the immune system and vesicle trafficking. The DUBs are attractive drug targets and have increasingly been implicated in cellular processes germane to malignancy which makes the continued characterisation of the role of DUBs during virus infection a worthwhile objective. In on-going experiments in the research group a DUB siRNA pools library screen identified 12 DUBs (USP1, USP4, USP5, USP34, USP45, USP46, OTUD6A, UCHL1, JOSD2, BRCC3 and MYSM1). Depletion of these hits in HeLa cells lead to an increase in cell viability following Semiliki Forest Virus (SFV) infection (and predicted to be pro-viral) and thus could potential be candidate antiviral targets. Inroads into understanding the role of the DUB hits during the alphavirus infection, focusing initial on the BSL2 model virus SFV, and extending this to CHIKV (at BSL3). In the present study, further screening focused on the deconvolution siRNA pools for the DUB hits. Investigation of the subsequent follow up experiments with one strong candidate DUB from this list, MYSM1. Two different approaches were taken. Firstly, the effect of depletion of MYSM1 by siRNA treatment was further investigated in HeLa cells. Secondly, the analysis was extended to investigate the role of MYSM1 in fibroblasts utilising MYSM1 genetic knockout murine embryo fibroblasts. Results from this study indicate that depletion of MYSM1 in HeLa cells by siRNAs resulted in a reduction in both SFV and CHIKV replication, as assayed by measuring RNA levels and plaque formation. It was also found that MYSM1 genetic knockout in MEF cells lead to increase in both SFV and CHIKV replication. In addition, depletion of MYSM1 by siRNAs in MRC-5 cells lead to increase in SFV replication. In conclusion, MYSM1 generated interesting data, implying a role during virus infection that appeared to depend on the cell type being infected. Up to now it is unclear what the effector mechanisms are that contribute to these observations, subject to further mechanistic and functional studies, may increase the options available for targeting this vital DUB during Alphavirus infections.
Urban Development refers to many topics such as: increased population density, city size, and individual’s production, distribution of technology and the growth of commercial, industrial and service professions. Such development is linked to the coordination of social and cultural trends in order to achieve social progress and economical prosperity. Knowledge as a topic now is known as intellectual capital wich led to upgrae the concept of urban development to be extended into many fields of knowledge, for example, cultural, social and human development to move the level of community culture into a new better standard.
The research adopted the urban transformation based on knowledge as an important factor in gr
... Show MoreCaptopril is an angiotensin converting enzyme inhibitor (ACEI) used to treat hypertension,
congestive heart failure, and myocardial infraction.
The only dosage form available for captopril is the plain tablet in strength of 12.5,25,50 and 100mg
tablet.
This investigation is concerned with factors affecting the formulation of captopril as a plain
tablet dosage form of 50mg. Many trials were made to prepare satisfactory tablets for the drug by
using wet – granulation methods with various additives. It was found that poly vinyl pyrrolidone
(P.V.P.) as binder gave the most satisfactory tablets. At the same time a shorter disintegrantion time
and slower dissolution rate were obtained with the addition of starch
The research included making a bibliography of the jurisprudential books available in the reference section of the central library at the University of Al-Mustansiriya. From this research, and I also saw that one of its objectives was to classify these books scientifically according to what was included in the Contemporary Islamic Fiqh Library of sections that were classified on its basis, according to what has settled in the custom of contemporary jurists, and according to the researcher’s view and his humble diligence, so the research was organized into an introduction and three topics. Each topic contained approximately five demands that included the sections of the contemporary jurisprudential lib
... Show MoreThis research aims at identifying the commitment of satellite news channels in Arabic to the set of important standards that reflect their credibility in dealing with the media material, and considering that these channels give special importance to events in Iraq, as well as the Arab region and the world, decide to choose them and study them with a problem The research was a question about the level of credibility of Iraqi media. This research is descriptive research, which used the survey method on an objective sample of 245 items, while the questionnaire was used as a data collection tool. Seven channels were selected in Arabic for the study. The three most watched channels were chosen. These channels included the channels of Russia t
... Show MoreContext has a significant impact on the interpretation of Qur'anic and literary texts, especially in ancient Arabic poetry since that language is no longer considered as a contemporary understandable language. Hence this research is entitled: (the impact of context on the morphological semantics in the Diwan of Abi Al-Aswad Al-Dau’ali) and the morphological meanings indicated by the morphological formula which lack the combination of other contextual clues. The researcher depended on the analytical approach to show the impact of pairing occurring between the contextual elements on determining the morphological meaning.
The most important findings reached at:
1- Context has a great impact in dispelling the possibilities arising fr
The structural, optical and electrical properties of ZnS films prepared by vacuum evaporation technique on glass substrate at room temperature and treated at different annealing temperatures (323, 373, 423)K of thickness (0.5)µm have been studied. The structure of these films is determined by X-ray diffraction (XRD). The X-ray diffraction studies show that the structure is polycrystalline with cubic structure, and there are strong peaks at the direction (111). The optical properties investigated which include the absorbance and transmittance spectra, energy band gab, absorption coefficient, and other optical constants. The results showed that films have direct optical transition. The optical band gab was found to be in the range t
... Show MoreAS Muhsen, International Journal of Psychosocial Rehabilitation (1475-7192), 2020 - Cited by 1
Many waste materials can be repurposed effectively within asphalt concrete to enhance the performance and sustainability of pavement. One of these waste materials is sawdust ash (SDA). This study explores the beneficial use of SDA as a substitute for limestone dust (LD) mineral filler in asphalt concrete. The replacement rate was 0%, 15%, 30%, 45%, and 60% by weight of total mineral filler. Scanning electron microscopy (SEM) was employed to assess the surface morphology of Sawdust (SD), SDA, and LD. In addition, a series of tests, including Marshall stability and flow, indirect tensile strength,moisture susceptibility, and repeated uniaxial loading tests, were conducted to examine the performance characteristics of asphalt mixtures of diffe
... Show MoreA polycrystalline CdTefilms have been prepared by thermal evaporation technique on glass substrate at room temperature. The films thickness was about700±50 nm. Some of these films were annealed at 573 K for different duration times (60, 120 and 180 minutes), and other CdTe films followed by a layer of CdCl2 which has been deposited on them, and then the prepared CdTe films with CdCl2 layer have been annealed for the same conditions. The structures of CdTe films without and with CdCl2 layer have been investigated by X-ray diffraction. The as prepared and annealed films without and with CdCl2 layer were polycrystalline structure with preferred orientation at (111) plane. The better structural pr
... Show MoreThe diversity of cultures is still the title of an Iraqi specificity that gave the society a diversity and this is reflected in the journalistic reality with the changing of the political system generate a new political and ideological life that differs from what is prevailed during the decades. However, its exacerbation of the degree of division is an additional duty for the press as a cultural platform and a knowledge bridge that contributes to the process of dialogue, addressing the differences, establishing a politically homogeneous structure through the state and socially by uniting all components of society and working to raise public awareness of the importance of national belonging to build a modern state. Cultural diversity is a
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